Glucose-Triggered Gelation of Supramolecular Peptide Nanocoils with Glucose-Binding Motifs

Sihan Yu, Zhou Ye, Rajdip Roy, Ravi R. Sonani, Irawan Pramudya, Sijie Xian, Yuanhui Xiang, Guoqiang Liu, Belen Flores, Einat Nativ-Roth, Ronit Bitton, Edward H. Egelman, Matthew J. Webber

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Peptide self-assembly is a powerful tool to prepare functional materials at the nanoscale. Often, the resulting materials have high aspect-ratio, with intermolecular β-sheet formation underlying 1D fibrillar structures. Inspired by dynamic structures in nature, peptide self-assembly is increasingly moving toward stimuli-responsive designs wherein assembled structures are formed, altered, or dissipated in response to a specific cue. Here, a peptide bearing a prosthetic glucose-binding phenylboronic acid (PBA) is demonstrated to self-assemble into an uncommon nanocoil morphology. These nanocoils arise from antiparallel β-sheets, with molecules aligned parallel to the long axis of the coil. The binding of glucose to the PBA motif stabilizes and elongates the nanocoil, driving entanglement and gelation at physiological glucose levels. The glucose-dependent gelation of these materials is then explored for the encapsulation and release of a therapeutic agent, glucagon, that corrects low blood glucose levels. Accordingly, the release of glucagon from the nanocoil hydrogels is inversely related to glucose level. When evaluated in a mouse model of severe acute hypoglycemia, glucagon delivered from glucose-stabilized nanocoil hydrogels demonstrates increased protection compared to delivery of the agent alone or within a control nanocoil hydrogel that is not stabilized by glucose.

Original languageEnglish
JournalAdvanced Materials
DOIs
StateAccepted/In press - 1 Jan 2023

Keywords

  • drug delivery
  • hydrogel
  • nanotechnology
  • supramolecular chemistry

ASJC Scopus subject areas

  • Mechanics of Materials
  • Mechanical Engineering
  • General Materials Science

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